The applicant seeks to establish a tenure-track academic career in the development of biomedical optical technologies to aid in the diagnosis, treatment, and understanding of human diseases, and especially cancer. He plans to develop advanced optical devices that are capable of imaging molecular function through targeted optical probes, utilizing such technologies in clinical and preclinical studies to improve patient outcomes. The applicant is a postdoctoral fellow in the Stanford University School of Medicine, where he is being trained in molecular imaging techniques in the research group of Dr. Chris Contag, a pioneer in this growing field that combines the latest developments in imaging, animal models, tumor biology, and molecular medicine. The Molecular Imaging Program at Stanford (MIPS), co-directed by Drs. Sam Gambhir and Chris Contag, is an ideal training ground for the applicant. This preclinical project combines technology development with biomarker discovery for functional image guidance during resection of meduloblastoma (MB), the most common pediatric brain tumor. A novel imaging technology, the dual-axes confocal microscope (DACM), will be developed to image fluorescent peptide probes that target MB biomarkers. A tabletop DACM will be used, along with targeted peptide probes, to image a spontaneous mouse tumor model of MB. A quantitative ratiometric-imaging method will be employed to improve tumor-to-normal image contrast, which will also be maximized by optimizing parameters such as imaging depth, probe concentration, and the procedure for rinse removal of unbound probe. A miniature DACM, which incorporates a 1 - 2 mm diameter gradient index "needle" lens, will be developed to guide MB debulking surgeries in mice. Improved resection will be demonstrated by quantifying residual tumor mass, and time-to-relapse, through bioluminescent imaging (BLI), and by monitoring overall survival. These technologies and methods will enable more complete and accurate resection of MB in the brain by allowing surgeons to deeply visualize tumor margins with cellular accuracy and molecular specificity. RELEVANCE: This project will develop a microscopic imaging tool, along with targeted contrast agents, to improve the ability of surgeons to remove brain tumors. Since the extent of tumor removal correlates with patient outcomes, and accurate resections are desired to prevent neurological damage, the potential impact on public health is far reaching.